Many of the cell-surface molecules which regulate immune responses contain conserved structural features similar to those found in immunoglobulin (Ig) . These molecules are encoded by genes that are presumed to have evolved from a common precursor and are therefore members of a large superfamily (Williams et al., Annu. Rev. Immunol 6:381-405 (1988)). Many of the Ig superfamily members are involved in cell-cell adhesion and signal transduction. While most members of this family contain multiple linearly-assembled Ig-like domains, several proteins have been identified that contain single Ig-like domains. Single Ig-like domain proteins that are known or assumed to be involved in cell-cell adhesion include: CD8.alpha. (Littman et al., Cell 40:237 (1985)), CD8.beta. (Johnson et al., Nature 323:74 (1986)), CD7 (Aruffo et al. , EMBO J. 6:3313 (1987)), Thy-1 (Williams et al., Science 216:696 (1982)), CD28 (Aruffo et al., Proc. Natl. Acad. Sci. USA 84:8573 (1987)), CTLA-4 (Brunet et al., Nature 328:267 (1987)) and Po which is a structural protein of the peripheral myelin sheath (Lemke et al., Cell 40:501 (1985)). In addition, others associate with the antigen receptors of B and T lymphocytes forming multimeric signal-transducing complexes including; CD3 .gamma., .delta. and .epsilon. chains (Gold et al. , Nature 321:431-434 (1986) ; van den Elsen et al. . Nature 312:413-418 (1984)), B29 (Hermanson et al., Proc. Natl. Acad. Sci., USA 85:6890 (1988)), and mB1 (Sakaguchi et al. , EMBO J. 7:3457-3464 (1988)).
Two single Ig-like domain containing proteins found on lymphocytes are preferentially associated with cellular activation and are known to be involved in mediating cell-cell interactions. CD28 is expressed much more on activated than nonactivated T and B lymphocytes (Turka et al., J. Immunol. 144:1646 (1990)), and CTLA-4 is expressed mostly, if not exclusively, by activated T and B lymphocytes (Brunet et al., Nature 328:267 (1987) ; Harper et al. , J. Immunol. 147:1037-1044 (1991)). The role of CD28 as a T cell receptor for the B7 molecule expressed by activated B cells has been recently identified (Linsley et al., Proc. Natl. Acad. Sci. USA 87:5031-503 (1990); Freeman et al., J. Immunol. 143:2714-2722 (1989)), as has a similar role for CTLA-4 (Linsley et al., J. Exp. Med. 174:561-569 (1991)). As with CD28 and B7, most of the Ig-like domain-containing receptors interact with other members of the Ig superfamily present on other cells.